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ABSTRACT. This work was conducted to determine whether aspirin and ibuprofen, when administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE 2 after postnatal closure. In the first experiment, a subcutaneous injection of PGE 2 (4 µg) was administered to newborn rats 3 hr after a Cesarean delivery from pregnant females which had been orally given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days 18, 19 and 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that maternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, inhibits the catabolism of PGE 2 and that the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, the key enzyme involved in catalyzing PGE 2 to convert it to its inactive metabolite 15-keto-PGE 2 , was not affected by maternal treatment with aspirin and ibuprofen. These results suggest that the increased ductal responsiveness to PGE 2 in newborn rats was a common response after maternal NSAID treatment, but the catabolism of PGE 2 in the lungs did not always contribute to this response. -KEY WORDS: neonatal lung, PGE 2 catabolism, re-opening.J. Vet. Med. Sci. 60(3): 377-379, 1998 females were caged individually thereafter.In the first experiment, the effect of prenatal aspirin and ibuprofen treatment on the re-opening of the DA induced by PGE 2 was examined. Aspirin (100, 300 mg/kg/day) and ibuprofen (10, 30 mg/kg/day) administration was carried out on days 18, 19 and 20 of gestation. Pregnant females given only saline served as the controls. Females were killed by decapitation at 1 p.m. on day 21 of gestation at least 24 hr after the last drug administration, and the newborn pups were immediately obtained by Cesarean delivery. Only male pups were used in this study. The pups were placed in a humid chamber at 37°C and maintained for 3 hr after the Cesarean delivery, at which time the DA would have been completely closed under normal conditions [5]. Then, each pup was given a subcutaneous injection of 4 µg of PGE 2 (Sigma Chemical Co., St. Louis) dissolved in 50 µl of physiological saline. The pups were returned to the same chamber until their DAs and pulmonary arteries (PAs) were measured. The calibrations were made 0, 15, 30, 60, 90 and 180 min after the injection.Each pup was rapidly frozen in an acetone-dry ice mixture at the time of death. The frozen pups were weighed and then 4 or 5 pups of similar weight were selected from each litter and stored for a couple of days at 20°C until the DA and PA were measured. Measurements were obtained by the whole-body freezing and shaving method described elsewhere [2], and the DA/PA ratio was obtained by previously described meth...

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The gubernaculum consists of the gubernacular cord connected with the vas deferens and the gubernacular bulb connected with the retroabdominal wall. The cord was first distinguished on day 15 of gestation. Its length reached the peak on day 16, followed by a reduction until day 18 to be almost constant thereafter. The bulb was first distinguished on day 16, and its length was steadily increased toward term. The testis began to descend with a reduced length of the cord. By day 19, the testis descended close to the caudal part of the bulb by the sharp bending of the cord. Microscopically, the bulb consisted at first of a centrally located mesenchymal mass and of a covering layer of myoblasts. Thereafter, the mesenchymal mass was gradually shifted toward the cranial part of the bulb, trailing loose mesenchymal tissue in the caudal part of the bulb. On day 19, the mass was decreased in cell population but increased in amount of collagen fibers. It is suggested that the testicular descent starts on day 16 together with the commencement of shortening of the gubernacular cord and enlargement of the gubernacular bulb.

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